Search for tag: "mice"

Interviewer: A social lifestyle with plenty of mental activity and exercise slows down cancer according to research in mice. We'll talk about that next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs, The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Melinda Angus-Hill, an investigator at the Huntsman Cancer Institute at the University of Utah. Dr. Angus-Hill, I really love this story. Your research is showing how a change in lifestyle can really impact the trajectory of cancer.

Dr. Angus-Hill: We have a mouse model that is meant to replicate colon cancer in humans. We've developed genetic mutations that profoundly influence the numbers of colon tumors that these animals get and we found that with enriched lifestyle, which includes improved social interactions with lots of other mice, they have huts and crawl balls and lots of things that they can do, lots of activities, they have wheels that they can run on, and we found that these improved social interactions and these things that they can do increase their lifespan of both males and females significantly.

Interviewer: By how much?

Dr. Angus-Hill: So, these mice, normally, begin to get sick with colon tumors at around three to four months old and they'll live two to three months longer than that with the environmental enrichment.

Interviewer: Which is pretty significant for a mouse?

Dr. Angus-Hill: Yes, very significant.

Interviewer: Like you mentioned, they're subject to a lot of changes compared to regular lab mice. I mean, you said they're around a lot of other mice, they're getting exercise, they're, you know, maybe just faced with a more interesting environment than they would usually have. Do you know if . . . it is a combination of those things that are impacting the mice or can you parse it out into one of those changes?

Dr. Angus-Hill: Well, I think it is actually all the entire environment that does this. There have been a lot of studies that have looked at exercise and the effects on tumor genesis and, basically, they give a single mouse a wheel and mice can run on the wheel as much as they like, and will often just spend the whole day running. They can run up to six kilometers a day under those conditions and that can actually be stressful on mice, but it will still have an effect on whether the size of the tumors decrease and whether the animals actually feel better. But it seems that this environmental enrichment is more a well-rounded approach where the animals, they can run if they like to, but there are many other things that they can do and that seems to improve in a different way than just running on a wheel.

Interviewer: So a lot of your work here which is really the advantage of working in mice or a model organism is trying to understand, you know, biologically, what's going on here. How is this environmental enrichment changing the biology of these mice? I mean, first of all, what's happening with the cancer? Is it not starting in the first place? Is it just progressing slower than cancer normally would? What are you seeing at that level?

Dr. Angus-Hill: Sure. It seems that we don't have a decrease in the numbers of tumors that actually initiate, which suggest that the genetic mutations that occur, you can't really stop them from occurring with environmental enrichment. However, it seems that we can actually make the tumors better. So, if a tumor can be better . . .

Interviewer: Yeah.

Dr. Angus-Hill: But the idea is that with environmental enrichment, there is less inflammation which results in what we think is, actually, a cause of a healing phenotype that occurs when the mice are environmentally enriched. So, basically, the tumors become more benign and they are less offensive. So, in the context of cancer, these tumors would be less likely to invade and metastasize, and become a serious problem.

Interviewer: Right. And you were talking about how it seems to trigger a wound healing process, which seems a little counterintuitive to me. I mean, what does wound healing have to do with cancer?

Dr. Angus-Hill: We were actually able to show that the animals, the male animals in particular, had an improved wounding process that happened in their colons. Basically, their tumors healed themselves with this environmental enrichment.

Interviewer: Like wound healing in our skin or . . .

Dr. Angus Hill: It's actually been most well-characterized in the skin and it has to go through multiple steps in order to complete the healing process, and so it has to get worse before it can get better. So there are several steps, including recruitment of inflammatory cells, increased angiogenesis which is making more blood vessels, and then, basically, the wound can resolve by re-epithelializing the cells and then, ultimately, a scar will be formed, and all of this will result in decreased inflammation.

So we saw decreased inflammation with environmental enrichment. This suggested to us that the colons and the colon tumor, this barrier that is normally essential for maintaining the . . . keeping the bacteria out, but also maintaining the normal cell structures in the colon were actually being helped with environmental enrichment.

Interviewer: I mean, this is really a different way of thinking about things. I mean, are you excited about sort of the possibilities here or . . .

Dr. Angus-Hill: Yeah. I think it's kind of a new idea that really, it's not super appealing to pharmaceutical industries, but it's something that everybody can take to heart and know that it's possible that reducing stress can actually improve your gut, you know, even just inflammation in general, and I think more studies are definitely needed to determine whether this translates to people, but you know, what harm is there in reducing stress? There are none. There are no harms to reducing your stress.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

Interviewer: Doing some spring cleaning and you come across some mouse droppings? Well, stop and listen to this podcast first before you do any more cleaning. That's next on The Scope.

Announcer: Health tips, medical news, research, and more for a happier, healthier life. From University of Utah Health Sciences, this is The Scope.

Interviewer: If you're doing some spring cleaning, maybe cleaning out the garage or an old attic, and you see some mouse or some sort of droppings, is that a concern? It turns out yes, it is, and there's a procedure you should go through if you do see that before you continue cleaning. Dr. Troy Madsen is an emergency room physician at University of Utah Health. What's the main concern here?

Dr. Madsen: The big concern here is something called hantavirus. This is a virus that mice carry. It's actually endemic to the four corners region, so southeastern Utah, but we've certainly seen cases in Salt Lake. There was a big outbreak of this virus at Yosemite several years ago. This is a virus that mice carry in their urine.

So the way people catch this virus is they're cleaning mouse droppings, they see some droppings, they sweep it up, sweep it into a dust pan. As they're sweeping, usually, where there are mouse droppings, there's also mouse urine, it aerosolizes this urine, this dry urine, kind of kicks it up into the air, they breathe it into their lungs, and then it can cause an extremely severe lung infection.

Very fatal, at least half of people who get this infection die from it. It's a bad thing to have. I personally know someone who had it who was cleaning his garage, caught the virus after cleaning. It's a big concern. Then you may ask, "Why is it a big concern this year in particular?" Because it's been a very, very wet winter, and when we have wet winters, the rodent population explodes.

This is exactly what happened at Yosemite several years ago when there was a big outbreak there. You get more mice around carrying this virus, more potential for exposure for humans, so we could potentially see cases of these.

Interviewer: If you see mouse droppings, that's the first hint that you need to do what we're about to talk about, is what do you about it, because you want to clean that mess up.

Dr. Madsen: Exactly. You're not just going to leave the mouse droppings. You've got to do something about it. Take some water, pour some bleach in it. It's kind of a 1 to 10 ratio. If you have a bucket of water, just get some bleach in that. You can then use that water and bleach in a spray bottle or pour it on the mouse droppings some way where you're getting the bleach on there, getting that area wet.

The reason this works is because you've got the bleach on there that's killing the virus. Then you've also got something wet on there. So when you wipe that up, it's not creating an aerosol. It's not creating something out of that dry urine that it gets in the air and you breathe in your lungs. That's the biggest thing for prevention.

Interviewer: So then you just target where you see the mouse droppings. You don't have to spray the solution on every surface in wherever you happen to be working?

Dr. Madsen: Exactly. If you're cleaning a garage, you figure if you're trying to get this solution all over, it's just not practical. Usually, where the mice have their droppings, that's where the urine is. My recommendation would be to have a spray bottle with you with the solution in it. If you're cleaning the garage, spray five or six squirts on that area. Let it sit for 5 to 10 minutes, then wipe it up, and you should be good at that point.

Interviewer: Okay, and wear a mask at the same time?

Dr. Madsen: Absolutely.

Interviewer: Would a mask alone stop it?

Dr. Madsen: Great question. I don't have a great answer. I think a mask would definitely help, would probably prevent it. I would still take the precautions with the solution though.

Interviewer: Let's say somebody didn't catch this in time, and now they're concerned that they have hantavirus. What are the symptoms?

Dr. Madsen: It's a little bit of a challenge because it probably feels at first like a bad cold, but then it progresses very rapidly to where you're having very significant difficulty breathing. It's one of those things where if you really have it, you'll probably know you have it, and you'll probably know pretty quickly.

Interviewer: A cold following some sort of a cleaning job in a place where this could have happened would be your first hint, and then go to the ER?

Dr. Madsen: Exactly. I would go to the ER for this. I don't want you to rush to the ER if you've been cleaning and then you get a little bit . . . some sniffles, but it's one of those things where it's something you would go to the ER for, anyway, because you would feel so sick and have so much trouble breathing. Even if you hadn't been cleaning, you would say, "Something's not right here."

Interviewer: Then what do you do to treat it?

Dr. Madsen: That's the challenge with it. Really, the treatment for it in the hospital is supportive care. We're helping people get through it while, hopefully, their body fights this off. Often, that means breathing for them, putting a tube in, and putting them on a ventilator to get them through this. In severe cases, that's what we have to do, but it's a challenge to treat.

Interviewer: So well worth avoiding?

Dr. Madsen: Absolutely. Try to avoid it.

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Interviewer: A new smart insulin could change diabetes treatment. Up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Danny Chou, USTAR assistant professor in biochemistry at the University of Utah. Dr. Chou, your discovery could really make a big difference in the lives of people with diabetes. Tell us about what you found.

Dr. Chou: So, we used a chemical approach to modify the native insulin molecule, and what we're trying to do is to have insulin that will be activated when the blood glucose level is high, so in the way that further regulate blood glucose level better for diabetic patients.

Interviewer: So, already, your work in mice would suggest that what you've developed is, I think, better than anything that's out there right now. Is that true?

Dr. Chou: Yes, because right now in the market, there are fast-acting insulins for meal-time use and there are long-acting insulins for basal level use. So basically there's no such insulin in the market right now that could provide any kind of glucose-regulated or glucose-responsive way.

Interviewer: And it seems like the results that you saw in mice were pretty striking. What did you see?

Dr. Chou: So what we see is that we could only do one single injection of this modified insulin, and then what we see is we could do three glucose tolerance test, which is kind of like a meal for the mice, and then we could see that one injection could be good for three different meals within a 13-hour span. So we really think this a very amazing and a very exciting result. But as we just mentioned, this right now is only in mice work and then we would try to see whether we could prove the safety of these insulins and one day we could put it into the clinical phase.

Interviewer: So, how long do you think it might take to get to the clinical phase?

Dr. Chou: So, we are thinking about a three-to-five year range.

Interviewer: For those of us who may not be familiar with living with diabetes, can you explain what some of the problems are that you're trying to address?

Dr. Chou: So, in the case of Type 1 diabetic patients, they do not have any insulin production inside their bodies. So, people with Type 1 diabetes, they have to totally rely on external source of insulin. And insulin is a drug that is not like you could put as much as possible and then you would still be okay. The thing is that you need to maintain your blood-glucose level in the normal range. So, when you inject too much insulin, that will give you a case of hypoglycemia, which will kind of cause dizziness, or in coma, or even death. So that's why people are afraid of injecting too much insulin inside a body.
However, if you do not inject enough insulin, that will give you a constant high-glucose levels, which is called hyperglycemia, and in the long run, that will lead to diabetic complications like kidney disease, eye blindness, or amputations. So, that's why we are trying to develop a special insulin in the way that its activity could be controlled by itself. So, basically, the activity is controlled by the blood-glucose levels inside your body. So, in that way, people with diabetes, they do not need to worry about the high or low glucose levels because the insulin itself is smart enough to control the glucose level inside a wide range.

Interviewer: You know, as it is, what you've developed is really incredible, but it sounds like you're also going to work on improving it.

Dr. Chou: Yes. So right now, I think we have already done a pretty good job in developing an insulin that could be used to reduce the high glucose level back to normal range during the meal time. But I think what we could still improve is in the hypoglycemic end. So what we try to do is we try to have the ideal insulin that the activity of insulin will be stopped or blocked when the glucose level is around, say, 80 milligram per [inaudible 00:04:33]. So, we will never need to worry about inducing hypoglycemia with this insulin injection.

Announcer: Interesting. Informative. And all in the name of better health. This is The Scope Health Sciences Radio.

Interviewer: A new practical method that will boost the productivity of genetic engineering labs, coming up next on The Scope.

Woman: Examining the latest research and telling you about the latest breakthroughs, The Science and Research Show is on The Scope.

Interviewer: Using principles borrowed from population biology, Dr. Luca Brunelli, an assistant professor in pediatrics at the University of Utah, has developed a rapid, inexpensive, one step method for isolating rare DNA recombinants. Dr. Brunelli, what motivated you to come up with this method?

Dr. Luca Brunelli: Our interest in these techniques really stems from our research focusing both on human genetics and mouse genetics and our interest in trying to use mice to elucidate key mechanisms of human disease.

Interviewer: This addresses an intermediate step in genetic engineering.

Dr. Luca Brunelli: Yes. We have described this technique that we call F.P.E., founder principle-driven enrichment, in E. coli in a technique that is commonly called recombineering or recombination mediated genetic engineering, which is an intermediate step that allows, for example, among many other things to produce the targeting vectors that are required to produce genetically modified mice.

Interviewer: What were some of the problems that you were trying to address?

Dr. Luca Brunelli: If one thinks of genetic combination, the general idea is that these events are rare. The key problem is the general conception that it's really impossible to isolate that one event out of a hundred thousand unless you link a marker to that event because of how rare it is.
In reality, we have found that by applying principles from population genetics, specifically the founder principle, you are able to very effectively, rapidly, cheaply, and simply isolate these rare variants without using markers. What population genetics and the founder principle tell us is that when you establish founder populations, meaning very small populations, from large populations some of these alleles, some of the genetic background that existed in the original population, either is wiped out or is enriched, is fixed in this new population.
As long as you have a screening technique, which in our case was P.C.R., to be able to detect whether in liquid cultures your event is present or not, what happens when you decrease the size of that culture to, let's say, 5000 cells is that in some of those liquid cultures you will still have one recombinant, but you've actually enriched for your recombinant for your rare event. So, going through two or three enrichment cycles such as this that I've just described you can actually isolate your variant, bring it to a frequency that is 1 in 20, 1 in 50, such that you can easily plate your liquid cultures on an agar plate and isolate the clone easily.

Interviewer: And just pick individual ones.

Dr. Luca Brunelli: Yeah, just picking the ones.

Interviewer: Basically, you're taking your original pool that has your recombinant in it, then you're diluting it out.

Dr. Luca Brunelli: How many days it's going to take to isolate your rare variant and how many P.C.R.s you're going to want to do really depends on your preference. In our manuscript we've actually included a mathematical model with a web available calculator that allows a researcher to sort of import their desired level of effort, if you will, and days that they want to do the isolation in, and be able to reselect the preferred conditions. The calculator will advise them on what kind of enrichment, what kind of dilution, to use under those circumstances.

Interviewer: Right. How much quicker is it?

Dr. Luca Brunelli: To generate something seamless you need to introduce both selection markers and counter selection markers, so at a minimum ten days. With our approach that takes us down to two to five days at the most.

Interviewer: Oh wow. And I imagine it's cheaper.

Dr. Luca Brunelli: Cheaper also, yes, because you save reagents, antibiotics, a number of...

Interviewer: I'm struck by this as really a very straightforward technique.

Dr. Luca Brunelli: It is, and what's striking in a way is that it had not been described before.

Interviewer: Exactly.

Dr. Luca Brunelli: I have to say that once we were developing this method and we thought to include the full mathematical model of this, we went to a mathematician to help us out with that. The first comment from the mathematician was well, this is so easy, why has nobody else thought about this before.

Interviewer: Yeah.

Dr. Luca Brunelli: It was extremely easy for the mathematician to understand that if you decrease the number of cells below a number that breaks the symmetry of how rare and more common variants are present it's pretty clear that you can enrich for those. Interviewer: What's the advantage over other selection techniques like zinc fingers or crispers?

Dr. Luca Brunelli: With zinc fingers and crispers people have used a different approach which is to create double stranded breaks in the DNA so the DNA would effectively make these changes at a much higher frequency. But the double stranded break, it's easy to understand, also creates, if you will, stress on the DNA and so has a chance to produce what people call off target effects . . .

Interviewer: I see.

Dr. Luca Brunelli: . . . making changes and modifications also in regions of the DNA where you wouldn't want to have those changes.

Interviewer: What are the applications for this method?

Dr. Luca Brunelli: One of the direct implications would be to ask the question whether what we have done in E. coli can also be replicated in mouse embryonic stem cells.
Other possible applications that we see that are really exciting are in recombineering pipelines with the idea of studying gene function, large scale modifications also, for example, to produce biofuels, so bacteria acquire certain characteristics that will enable them to perform better at certain functions like to do production of a biofuel or cleaning water or whatever you might think of.
Although it's outside of the medical field, we're certainly interested in some of those applications, and we are considering possibly collaborating with some investigators who work in those fields.

Woman: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.